The present invention relates to novel medicinal herbal compositions and their use for treating patients with immunological disorders, particularly IgE mediated diseases, which include, but are not limited to, allergic rhinitis, allergic conjunctivitis, allergic asthma, atopic eczema, atopic dermatitis, food allergy, hyper IgE syndrome, and rheumatoid arthritis. The present invention also relates to methods for making the medicinal herbal compositions and the method for treating patients with the medicinal herbal compositions.
Antigen-induced, particularly allergen-induced immunological disorders, such as asthma, has long been known as one of the serious health problems in the world. Allergy in one form or another afflicts more than 20% of the world population. In recent years, statistics shows that the onset of the allergic-related immunological disorders has shifted to the younger population, which means that more children and/or adolescents have developed symptoms of allergen-induced immunological disorders. For instance, in Taiwan, the prevalence of childhood asthma increased from 1.3% in 1974, to 5.07% in 1985, and to 5.8% in 1991. Also, allergic rhinitis increased from 7.84% in 1985 to 20.67% in 1991. Furthermore, atopic eczema was 1.43% in 1974 and 1.23% in 1985, in 1991, it was 3.84%. It is believed that the early onset of allergen-related immunological disorders are likely due to environmental pollution.
Respiratory allergies are immunoglobulin E (IgE)-mediated immune response. (See Brinker, J. Naturopathic Medicine, (1993):4:64-68). There are two major types of respiratory allergic reactions: The immediate hypersensitivity reactions include allergic rhinitis (hay fever) and allergic (extrinsic) bronchial asthma. Allergic rhinitis is brought on by antigen/IgE binding to sensitized mast cells and basophils, causing a decrease in cAMP which leads to release of esosinophil chemotactic factor and histamine. Histamine binding to H1-receptors has several results. It increases vasodilation, capillary permeability, and smooth muscle contraction, manifesting as nasal congestion with watery discharge, sneezing, and itching eyes.
Allergic asthma is another IgE-mediated immune response in which mast cells release histamine, bradykinin, and arachidonic acid metabolites including the leukotriene slow reacting substances of anaphylaxis and thromboxane/prostaglandin bronchoconstrictors. Platelet activating factor is another potent asthma mediator released from a number of leukocytes. In this condition, histamine, which released after a decrease in cAMP, acts on H1-receptors to cause bronchospasm. It is also responsible for bronchoconstriction due to cholinergic reflex action and half of the prostaglandin generation in anaphylaxis.
While the percentage of affected population and severity of the diseases are rising, current methods for treating allergy still primarily depend on empirical and serendipitous findings rather than from scientific approach. At present, most patients are treated with drugs that aim at controlling symptoms resulted from the release of mediators by effector cells. Although some drugs appear to be effective in short term and with few occurrences of adverse effects, long term effects for preventing disease progression and permanent destruction are still largely unknown. For example, long-term oral therapy, such as steroid therapy, for treating asthma, is now known to be associated with multiple debilitating effects such as growth delay, osteoporosis, and adrenal suppression.
Traditional Chinese herbs and medicinal combinations have been known for improving function of immune system and treating various chronicle immunological disorders. For example, Hamasaki et al., J. Ethnopharmacology, (1997) 56:123-131, disclose a Chinese herbal medicine, Shinpi-To, which inhibits IgE-mediated leukotriene synthesis in rat basophilic leukemia-2H3 cells. Shinpi-To is a freeze-dried granular Chinese herbal medicine prepared from extract of seven (7) medicinal herbs, i.e., Ephedrae herba (Ephedra sinica Stapf), Armeniacae semen (Prunus armeniaca Linne), Magnoliae cortex (Magnolia obovata Thunberg), Aurantii nobilis Pericarpium (Citrus unshiu Markovich), Glycyrrhizae radix (Glycyrrhiza uvalensis Fischer), Bupleuri radix (Bupleurum falcatum L.), and Perillae herba (Perilla frutescens Britton var. acuta Kudo). Shinpi-To is useful for treating childhood asthma.
Toda et al., J. Ethnopharmacology, (1988) 24:303-309, discloses a Chinese herbal medicine, Saiboku-To, which shows inhibitory effects on histamine release from mouse peritoneal mast cells. Saiboku-To is useful for treatment of asthma. Saiboku-To contains ten medicinal herbs: Bupleurum falcatum L., Pinellia ternata Breitenbach, Poria cocos Wolf, Scutellaria baicalensis Georgi, Zizyphus vulgaris Lam., Panax ginseng C. A. Meyer, Magnolia oborata Thumberg, Glycyrrhiza glabra L., Perilllae frutescens Britton var. acuta Kudo, and Zingiber officinale Roscoe.
Li et al., Immunopharmacology, (1999), 43:11-21, discloses a Chinese herbal medicine, Hochu-Ekki-To, which shows effects on restoring stress-induced immunosuppression. Hochu-Ekki-To consists of ten (10) ingredients, i.e., Ginseng Rx., Atractylodis alba Rz., Astragali Rx., Angelicae sinensis Rx., Jujubae Fr., Citri reticulatae Pc., Bupleuri Rx., Glycyrrhizae Rx. Preparata, Zingiberis recens Rz., and Cimicifugae Rz.
Zou et al., Chinese Traditional and Western Medical Magazine, (1996):529-532, discloses a Chinese herbal medicine, Wenyang Tongluo mixture, for treating cold-type asthma patients. It shows effects on improving pulmonary ventilation functions, regulating adrenergic xcex2-receptors of peripheral blood lymphocytes, and decreasing the serum level of 5-hydroxytryptamine. Wenyang Tongluo mixture contains twelve (12) medicinal herbs, i.e., Red Ginseng, Zhi Fu Pian, Yin Yang Huo, Dried Ginger (Zingiberis recens Rz.), Zhi Huang Zhi, Angelicae sinesis Rx., Ephedra, Polygalae Rx., Sang Baipi, Sheng Shi Gao, Schisandrae Fr., and Licorice (Glycyrrhizae Rx. Preparata).
There is also an ophiopogon decoction disclosed on the internet (www.herb.com.tw) which shows a combination of six (6) herbs, i.e., Ophiopogonis Rx., Pinelliae Rz. Preparata, Oryzae Sm., Jujubae Fr., Ginseng Rx., and Glycyrrhizae Rx. It is useful for treating bronchitis and bronchial asthma.
In dealing with Chinese herbal medicine, it is critical to control the quality of the herbs, because the contents and/or active ingredients of the herbs can vary significantly due to herb""s growing conditions and harvesting seasons/techniques. If any of the critical conditions and factors, such as the locality where the herbs are grown, the season(s) when the herbs can be harvested, and the manufacturing process of the herb, are not met, the effectiveness of the herbal medicine would vary. So far, there has been no report showing the adoption of any reliable scientific method for monitoring the quality of the Chinese herbal medicine.
The present invention provides novel and non-toxic pharmaceutical compositions derived from herbs which are primarily found in China and Taiwan. The combined use of these herbs has never been found in any literatures or reports. These pharmaceutical compositions are particularly effective in treating patients with immunological disorders, especially IgE mediated diseases. The pharmaceutical compositions of the present invention have demonstrated special effects on down-regulation of the synthesis of interleukin 4 (IL-4) and suppression of IgE. In addition, to effectively control the quality of the herbs, the present invention fingerprints each herb using thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) to ensure that each herb used in the composition contains consistent and reproducible ingredients.
The present invention provides pharmaceutical compositions which contains a variety of Chinese herbs. The pharmaceutical compositions contain, as essential herbs, Ophiopogon (Tuber ophiopogonis), Pinellia (Tuber Pinelliae), and raw Licorice (Radix Glycyrrhizae). The preferred weight ratio of ophiopogon: pinellia: raw licorice is 3:2:1. The fourth herb is either tang-shen (Radix Codonopsitis) or American ginseng (Radix Pancis Quinquefolii). The final herb is selected from a group of three (3) herbs which are lantern tridax (Herba Tridacis procumbentis), Taiwan Adenostema (Herba Adenostemmatis), and Heartleaf houttuynia (Herba Houttuyniae). Taiwan Adenosterma and Heartleaf houttuynia, can only be found in Taiwan. Lantern tridax can be found in Taiwan and South America. Among these pharmaceutical compositions, the most preferred composition contains ophiopogon, pinellia, raw licorice, American ginseng, and lantern tridax. The preferred weight ratio of ophiopogon:pinellia:raw licorice:tang-shen (or American ginseng):lantern tridax (or Taiwan Adenostema or heartleaf houttuynia) is 3:2:1:1:1.
The method for preparing the pharmaceutical composition is as follows: First, except for ophiopogon, all of the herbs are cut into pieces, dehydrated, ground, and passed through a sieve to produce herbal powder. The pharmaceutical ingredients in ophiopogon are extracted by boiling and condensing ophiopogon in water. The ophiopogon extract (filtrate) is then obtained by passing the condensed ophiopogon-water mixture through a sieve. Second, the ophiopogon filtrate is mixed with the herbal power to form a herbal mixture. This herbal mixture is then placed into a fluidized granulation machine for the production of granules. The granules can optionally be sieved to produce granules with uniform size. The granules can be further encapsulated. The pharmaceutical compositions are particularly effective in treating patients with immunological disorders, particularly IgE mediated diseases, which include, but are not limited to, allergic rhinitis, allergic conjunctivitis, allergic asthma, atopic dermatitis, food allergy, hyper IgE syndrome, atopic eczema, and rheumatoid arthritis.
Finally, the present invention employs a method to ensure the quality of the herbs used for the preparation of the composition. Each herb is fingerprinted using high performance liquid chromatography (HPLC). Therefore, if the quality of the herbs changes, such as due to growing conditions (too much rain or draught) or harvesting time, they can be detected by studying the profiles of the HPLC chromatograms. In addition to HPLC, a thin-layer chromatography (TLC) method is also adopted.